Effects of low molecular weight B-cell growth factor on proliferation of leukemic cells from children with B-cell precursor-acute lymphoblastic leukemia.
Recently, low-molecular-weight B-cell growth factor (LMW-BCGF) has been reported to stimulate growth of leukemic cells from B-cell precursor-acute lymphoblastic leukemia (BCP-ALL). We further investigated the effects of LMW-BCGF on proliferation of leukemic clonogenic (progenitor) and nonclonogenic (progeny) cells from children with BCP-ALL (28 patients) and B-cell ALL (two patients). Patients were either at diagnosis (n = 18) or in relapse (n = 12). Response of leukemic progenitor cells was determined by culturing cells (10(5) cells/mL) in methylcellulose with 0.1 U/mL LMW-BCGF. Colonies (greater than 20 cells) were counted at day 7. The response of the leukemic progeny population was determined by DNA synthesis studies using tritiated-thymidine and by DNA quantitation with propidiumiodide for determination of cell-cycle status. LMW-BCGF supported growth of leukemic progenitor cells from 20 of 28 (71%) BCP-ALL and two of two B-cell ALL patients. Colony numbers ranged from 7 to 2,400 (mean 145, median 45). A dose-response effect in colony growth was noted, with an apparent plateau at approximately 2.0 U/mL LMW-BCGF. Colony cells were primarily of leukemic phenotype (CD19+/CD10+/-). LMW-BCGF also induced significant increases in leukemic progeny cell proliferation as measured by both thymidine incorporation (stimulation indexes of 1.6 to 34) and by cell-cycle assay (percentage S+ G2/M stimulation indexes of 1.6 to 6). LMW-BCGF was more effective in stimulating leukemic proliferation than three recombinant interleukins (rIL-2, rIL-3, rIL-4), although rIL-3 was able to support colony growth in 4 of 11 patients. These results indicate that LMW-BCGF and, to a lesser degree rIL-3, are able to stimulate proliferation of BCP-ALL progenitor and progeny cells, whereas rIL-2 and rIL-4 do not support progenitor cell proliferation and have only marginal effects on leukemic progeny cell proliferation.
Findley
H W
HW
Division of Pediatric Hematology/Oncology, Emory University, Atlanta, GA 30322.
Zhou
M X
MX
Davis
R
R
Abdul-Rahim
Y
Y
Hnath
R
R
Ragab
A H
AH
D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002051:Burkitt Lymphoma / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology* / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
D007376:Interleukin-2; D007377:Interleukin-3; D008222:Lymphokines; C058162:low molecular weight-B cell growth factor; D015847:Interleukin-4; D004247:DNA; D013936:Thymidine